Severity Of Major Depressive Disorder Research Articles

A Choice-Based Conjoint Analysis of the Psychiatrist Decision-Making Process Used in Determining When to Discharge Adults With Major Depressive Disorder Hospitalized for Active Suicidal Ideation With Intent.

To ascertain the relative importance of attributes considered when deciding to discharge patients hospitalized with major depressive disorder (MDD) and active suicidal ideation with intent, a choice-based conjoint analysis was conducted via online survey among US-based psychiatrists actively managing such patients. Potential attributes and attribute levels were identified. Attribute importance in decision to discharge and the discharge time frame were assessed. One hundred psychiatrists completed the survey. The relative importance of attributes were current MDD severity (relative importance weight [out of 100] 24.8 [95% confidence interval, 23.3-26.3]), clinician assessment of current suicidal ideation (20.8 [18.5-23.0]), previous history of suicide attempts (16.7 [15.9-17.6]), psychosocial support at discharge (13.0 [11.7-14.4]), postdischarge outpatient follow-up (9.8 [8.8-10.8]), current length of hospital stay (9.2 [8.1-10.3]), and suicidal ideation at admission (5.7 [4.8-6.6]). Thus, current clinical symptoms were considered the most important attributes by psychiatrists when discharging patients initially hospitalized with MDD and active suicidal ideation with intent.

Influence of antidepressants on plasma levels of nitric oxide metabolites in patients with major depressive disorder.

The impairment of endothelial function by reduced endothelial production of nitric oxide (NO) may contribute to the increased risk of developing cardiovascular disease in patients with depression. NO also plays an essential role in the efficacy of antidepressants. The present study aimed to confirm our previous preliminary findings using a larger sample and different antidepressants. We enrolled 100 patients with major depressive disorder (MDD) and 50 healthy controls. Patients were administered sertraline, duloxetine or mirtazapine and were followed up for 8 weeks. We also compared the rate of increase in plasma levels of metabolites of NO (NOx) among the three antidepressant treatments. Baseline plasma NOx levels were significantly lower in the MDD group than in the control group. A negative correlation was found between plasma NOx levels and the severity of MDD. Treatment with duloxetine significantly increased plasma NOx levels, whereas sertraline treatment caused no significant increase.

Correlation between S100B and severity of depression in MDD: A meta-analysis

Background Previous studies have demonstrated elevated levels of the S100B protein (located in glial cells) in major depressive disorder (MDD) as compared to healthy controls. However, studies reporting correlation between S100B levels and depression severity have been conflicting. Methods We investigated, through systematic review and meta-analysis, whether the correlation between S100B levels and depression severity is significant in patients with MDD. Pearson correlation coefficients reported in the individual studies were converted to Fisher’s Z scores, then pooled using the random effects model. Meta-regression was used to test modifiers of the effect size. Results Sixteen studies including 658 patients with MDD met eligibility criteria. No publication bias was observed. There was a significant and positive correlation between serum S100B level and depression severity (r = 0.204, z = 2.297, p = 0.022). A meta-regression determined that onset age of MDD and percentage of female participants are significant modifiers of this correlation. A moderate, but non-significant heterogeneity was observed in serum studies (44%). Conclusion As many studies have reported significantly increased levels of S100B in MDD compared to controls, this meta-analysis supports the assumption that the increase in S100B correlates with the severity of MDD. Additional studies investigating the precise biological connection between S100B and MDD are indicated.

Neural Activation via Acupuncture in Patients With Major Depressive Disorder: A Functional Near-Infrared Spectroscopy Study

Background and Objective: Acupuncture is used as an alternative treatment for patients with major depressive disorder (MDD). The associated therapeutic effect of acupuncture is often attributed to its modulatory effect on the activity of the pre-frontal cortex (PFC), although the mechanism is not well-studied. We employed a repeated measures design to investigate the brain modulatory effect of acupuncture on the PFC in a group of patients with MDD and investigated whether the modulatory effect is influenced by the severity of the disease.Methods: A total of 47 patients diagnosed with MDD were enrolled in this functional near-infrared spectroscopy experiment. The severity of depressive symptoms was measured at baseline using the Hamilton Depression Rating Scale-24 (HAMD). The cortical activation in the bilateral PFC areas during a verbal fluency task (VFT) was measured before and after a single session of acupuncture in the Baihui acupoint. We further explored the potential correlation between the severity of MDD and task-related activation before and after acupuncture.Results: A single session of acupuncture significantly tended to enhance the activation level of the left frontopolar cortex in patients with severe depression during VFT, but a null effect was found in those with mild to moderate depression. Among patients with severe depression, a strong correlation was observed between HAMD scores and the change in VFT-related activation after acupuncture in the left dorsolateral PFC (DLPFC).Conclusion: A single session of acupuncture did not significantly modulate the activation of the left PFC in patients with mild to moderate depression; however, it demonstrated a tendency to enhance the activation of the frontopolar area in patients with severe depression. Among patients with severe depression, there is a correlation between the activation by acupuncture of left DLPFC during executive functioning and the severity of depressive symptoms, suggesting that the brain activity induced by acupuncture is likely to be influenced by the baseline disease severity in patients with MDD.

Circadian preference and sleep quality in healthy controls and psychiatric inpatients with major depressive disorder – An actigraphy study incorporating morning and evening mood assessments

ABSTRACT Major depressive disorder (MDD) is frequently accompanied by sleep disturbance. Regarding diurnal preference (chronotype), sleep problems and low mood have been associated with evening orientation. Considering diurnal preference, we investigated subjective restorative value of sleep and actigraphy sleep parameters together with mood assessments twice a day, i.e. in the morning and evening, during weekdays and weekends in MDD psychiatric inpatients and healthy controls (HCs). The restorative value of sleep was higher during the weekend in HC, and bedtimes and risetimes were delayed during the weekend compared to weekdays in HC and MDD. Morning mood affected subjective sleep ratings in both groups, while association with symptom severity (BDI) in MDD remained insignificant. In HC, better evening mood was associated with later bedtimes. Regarding the chronotype in HC, evening orientation was associated with relatively low restorative value of sleep during weekdays, and morning orientation was associated with relatively higher actigraphy sleep efficiency during weekdays compared to weekend. In MDD, an association of evening orientation with later rise times could be observed, while no chronotype dependent effect emerged regarding the restorative value of sleep or sleep efficiency. Our results emphasize that research on sleep in MDD should incorporate weekdays as well as weekends, chronotype assessment, and measures of morning and evening mood, as these can be associated with ratings of the subjective restorative value of sleep (i.e. in our study, better morning mood was associated with higher restorative values), but also with behavioral sleep parameters (i.e. in our study, more positive evening mood was associated with later bedtimes). Potentially, the restorative value of sleep in MDD evening types can be improved by maintaining a regular sleep schedule, which needs to be investigated in an experimental design.

EEG-based Major Depressive Disorder Detection Using Data Mining Techniques.

Major depressive disorder (MDD) is a common mental illness characterized by a persistent feeling of low mood, sadness, fatigue, despair, etc.. In a serious case, patients with MDD may have suicidal thoughts or even suicidal behaviors. In clinical practice, a widely used method of MDD detection is based on a professional rating scale. However, the scale-based diagnostic method is highly subjective, and requires a professional assessment from a trained staff. In this work, 92 participants were recruited to collect EEG signals in the Shenzhen Traditional Chinese Medicine Hospital, assessing MDD severity with the HAMD-17 rating scale by a trained physician. Two data mining methods of logistic regression (LR) and support vector machine (SVM) with derived EEG-based beta-alpha-ratio features, namely LR-DF and SVM-DF, are employed to screen out patients with MDD. Experimental results show that the presented the LR-DF and SVM-DF achieved F 1 scores of 0:76 0:30 and 0:92 0:18, respectively, which have obvious superiority to the LR and SVM without derived EEG-based beta-alpha-ratio features.

Effects of Repetitive Transcranial Magnetic Stimulation on Frontal-Thalamus Circuit in Schizophrenic Patients

During depressive episode, bipolar disorder (BD) patients share indistinguishable depression symptoms with major depressive disorder (MDD).However, whether neural correlates underlying the anhedonia, a core feature of depression, is different between BD and MDD remains unknown. To explore neural correlates underlying the anhedonia in BD and MDD, structural T1-weighted images from 36 depressed BD patients, 40 depressed MDD patients matched for depression severity and 34 health controls (HCs) were scanned. Considering the vital role of nucleus accumbens (NAc) in the anhedonia, we constructed the structural covariance network of NAc for each subject. Then, we explored altered structural covariance network of NAc and its interaction with the anhedonia severity in BD and MDD patients. As a result, BD and MDD patients shared decreased structural covariance of NAc connected to prefrontal gyrus, bilateral striatum extending to bilateral anterior insula. Apart from these regions, BD patients presented specifically increased structural covariance of NAc connected to left hippocampus extending to thalamus. The interaction between structural covariance network of NAc and the anhedonia severity in MDD was mainly associated anterior insula (AIC), amygdala, anterior cingulate cortex (ACC)and caudate while that in BD was mainly located in striatum and prefrontal cortex. Our results found that BD and MDD patients presented commonly and distinctly altered structural covariance network of NAc. What is more, the neural correlates underlying the anhedonia in BD and MDD might be different.

Glial fibrillary acidic protein as blood biomarker for differential diagnosis and severity of major depressive disorder

Neuroinflammation has been connected to the pathophysiology of major depressive disorder (MDD) and neurochemical biomarkers of glial pathology could aid the diagnosis and might support patient stratification and monitoring in clinical trials. Our study aimed to determine the utility of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, for the differential diagnosis and monitoring of MDD. Employing Simoa technology we measured levels of GFAP in prospectively collected serum samples from 81 age-matched patients with MDD, schizophrenia (SZ), bipolar disorder (BP), and healthy controls (HC). Highest GFAP levels were determined for MDD. At a cut-off of 130 pg/ml, MDD could be discriminated with 87% sensitivity from SZ and BP (specificity 70%) and from HC (specificity 56%). GFAP levels increased with age (r = 0.5236, p = 0.0002) and with MDD severity quantified based on the Montgomery-Åsberg Depression Rating Scale (r = 0.4308, p = 0.0221). Neurofilament light chain serum levels were not different in the diagnostic groups and not associated with GFAP levels (r = 0.0911, p = 0.576) pointing to an independence of astrocyte activation on neurodegeneration. Our study provides first evidence that serum GFAP levels could improve the differential diagnosis of MDD and that depression severity could be objectively quantified using serum GFAP levels. Furthermore, serum GFAP might represent a marker to monitor astroglial pathology in the course of MDD.

Inflammation mediates depression and generalized anxiety symptoms predicting executive function impairment after 18 years

IntroductionScar theories propose that elevated depression and anxiety can predispose people to future decreased executive function (EF) via heightened inflammation across decades. However, more longitudinal (versus cross-sectional) research on this topic is needed. ObjectiveWe thus investigated if increased major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) severity predicted EF decrement 18 years later via heightened inflammation. MethodCommunity-dwelling adults participated in this study. Time 1 (T1) MDD, GAD, and PD severity (Composite International Diagnostic Interview–Short Form), T2 inflammation (interleukin-6, C-reactive protein, and fibrinogen blood levels concentration), and T2 and T3 EF (Brief Test of Adult Cognition by Telephone) were measured. The waves of assessment were spaced approximately 9 years apart. Structural equation modeling was conducted. ResultsHigher T1 MDD and GAD (but not PD) severity forecasted elevated T2 inflammation (Cohen's d = 0.116–0.758). Greater T2 inflammation level predicted lower T3 EF following 9 years (d = -0.782–-0.636). The T1 MDD–T3 EF and T1 GAD–T3 EF negative associations were mediated by T2 inflammation, and explained 38% and 19% of the relations, respectively. Direct effects of higher T1 GAD and MDD predicting lower T3 EF were also observed (d = -0.585–-0.560). Significant effects remained after controlling for socio-demographic, lifestyle, medication use, various illness variables across time, and T2 EF. ConclusionsInflammation may be a mechanism explaining the T1 MDD–T3 EF and T1 GAD–T3 EF relations. Treatments that target inflammation, worry, and/or depression may prevent future EF decline.

Does Symptom Linkage Density Predict Outcomes in Cognitive Therapy for Recurrent Depression?

Acute-phase cognitive therapy (CT) is an efficacious treatment for major depressive disorder (MDD), but how CT helps patients is incompletely understood. As a potential means to clarify CT mechanisms, we defined "symptom linkage density" (SLD) as a patient's mean time-lagged correlation among nine depressive symptoms across 13 weekly assessments. We hypothesized that patients with higher SLD during CT have better outcomes (treatment response, and fewer symptoms after response), and we explored whether SLD correlated with other possible CT processes (growth in social adjustment and CT skills). Data were drawn from two clinical trials of CT for adult outpatients with recurrent MDD (primary sample n = 475, replication sample n = 146). In both samples, patients and clinicians completed measures of depressive symptoms and social adjustment repeatedly during CT. In the primary sample, patients and cognitive therapists rated patients' CT skills. After CT, responders were assessed for 32 (primary sample) or 24 (replication sample) additional months to measure long-term depression outcomes. Higher SLD predicted increases in social adjustment (both samples) and CT skills (primary sample) during CT, CT response (both samples), and lower MDD severity for at least 2 years after CT response (both samples). Analyses controlled patient-level symptom means and variability to estimate SLD's incremental predictive validity. These novel findings from two independent samples with longitudinal follow-up require further replication and extension. SLD may reflect or facilitate generalization of CT skills, improvement in social functioning, or other processes responsible for CT's shorter and longer term benefits.

Ventromedial prefrontal cortex/anterior cingulate cortex Glx, glutamate, and GABA levels in medication-free major depressive disorder

Glutamate (Glu) and gamma-aminobutyric acid (GABA) are implicated in the pathophysiology of major depressive disorder (MDD). GABA levels or GABAergic interneuron numbers are generally low in MDD, potentially disinhibiting Glu release. It is unclear whether Glu release or turnover is increased in depression. Conversely, a meta-analysis of prefrontal proton magnetic resonance spectroscopy (1H MRS) studies in MDD finds low Glx (combination of glutamate and glutamine) in medicated MDD. We hypothesize that elevated Glx or Glu may be a marker of more severe, untreated MDD. We examined ventromedial prefrontal cortex/anterior cingulate cortex (vmPFC/ACC) Glx and glutamate levels using 1H MRS in 34 medication-free, symptomatic, chronically ill MDD patients and 32 healthy volunteers, and GABA levels in a subsample. Elevated Glx and Glu were observed in MDD compared with healthy volunteers, with the highest levels seen in males with MDD. vmPFC/ACC GABA was low in MDD. Higher Glx levels correlated with more severe depression and lower GABA. MDD severity and diagnosis were both linked to higher Glx in vmPFC/ACC. Low GABA in a subset of these patients is consistent with our hypothesized model of low GABA leading to glutamate disinhibition in MDD. This finding and model are consistent with our previously reported findings that the NMDAR-antagonist antidepressant effect is proportional to the reduction of vmPFC/ACC Glx or Glu levels.

Cytokine Levels Post Acute Exercise In Individuals With Major Depressive Disorder

Individuals with Major Depressive Disorder (MDD), particularly those with more severe depression, often suffer from chronic inflammation. After high-intensity exercise, cytokine concentrations increase in the blood-stream, though moderate intensity exercise results in limited cytokine changes in healthy adults. As inflammation appears dysregulated as MDD severity increases, the extent and magnitude of the inflammatory response to moderate exercise may be augmented by MDD severity, though this is largely untested. PURPOSE: To evaluate cytokine levels during and for up to 50-minutes after moderate exercise in adults with MDD and evaluate the effect of depression severity on cytokine changes. METHODS: Adults (n = 15) with MDD completed a demographic survey and the Patient Health Questionnaire-9 before completing a 30-minute moderate exercise session (Borg’s rating of perceived exertion = 13) on a stationary bike. Blood samples were collected before, mid, immediately after, 25-, and 50-minutes post-exercise. Serum was allowed to clot before being centrifuged, aliquoted, and frozen until cytokine quantification (IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, GM-CSF, IFNgamma, and TNF-alpha) via MILLIPLEX® MAP kit. Low/high depression severity was determined based on PHQ-9 (low: 0-9; high: ≥10). A 2 severity (low/high) by 5 time (pre, mid, post, 25-, and 50-minute post) repeated measures ANOVA was conducted to evaluate cytokine changes across time and by severity group. RESULTS: There was a significant effect of depression severity on IFNgamma [F(1, 65) = 9.26, p < .003)], IL-10 [F(1, 65) = 8.95, p < .003)], IL-12p70 [F (1, 65) = 12.77, p < .001], IL-1beta [F(1, 65) = 6.51, p < .01], IL-2 [F (1, 65) = 13.67, p < .001], and IL-7 [F(1, 65) = 19.63, p < .001], while there were no significant main effects of time or severity by time interactions. CONCLUSIONS: While confirming a depression severity-inflammation link, these findings show a lack of support for an acute inflammatory response to moderate exercise indicating a normal response to moderate exercise in these adults with MDD regardless of depression severity. Along with past research showing the antidepressant effects of moderate exercise in MDD our findings support the use of moderate exercise for symptom management or treatment of MDD.

Relationship between initial self-perceived depressive symptoms and disease severity in working patients with first-onset major depressive disorder.

The severity of major depressive disorder (MDD), which is related to the depressive symptoms, is a predictor of clinical outcomes and may be used to determine the appropriate treatment. However, there is a lack of systematic research on the relationship between early depressive symptoms and MDD severity. This study aimed to clarify the association between initial depressive symptoms and MDD severity in working patients. We assessed 118 patients aged over 20 years who visited the Neuropsychiatry Department of the Osaka City University Hospital following their first episode of MDD. Logistic regression analyses were performed to estimate the odds ratios (OR) with 95% confidence intervals (CI) for the associations between age, gender, marital status, working hours, and initial self-perceived depressive symptoms and MDD severity. Age and working hours were analyzed as continuous variables, and gender (man, woman), marital status (married, single) and severity (mild to moderate MDD, severe to very severe MDD) were analyzed as categorical variables. The most common initial self-perceived symptom was "depressed mood," followed by "fatigue or loss of energy nearly every day." The univariate analysis found no association between age, gender, marital status, or working hours and MDD severity. Initial self-perceived non-somatic symptoms were associated with increased odds of having severe MDD (odds ratio = 3.32, 95% confidence interval 1.46-7.58), and this association persisted in the adjusted model (odds ratio = 3.35, 95% confidence interval 1.47-7.60). Initial self-perceived non-somatic depressive symptoms are significantly associated with MDD severity at its first onset. Workplace support may lead to the early detection and treatment of working patients with non-somatic symptoms.

Disruption of Neural Activity and Functional Connectivity in Adolescents With Major Depressive Disorder Who Engage in Non-suicidal Self-Injury: A Resting-State fMRI Study.

Background: Non-suicidal self-injury (NSSI), which commonly occurs during adolescence, often co-occurs with major depressive disorder (MDD). However, the underlying neurobiological mechanisms in adolescents with MDD who engage in NSSI remain unclear. The current study examined the aberrant local neural activity in certain areas of the visual regions and the default mode network (DMN) and the resting-state functional connectivity (rs-FC) in changed brain regions in adolescents with MDD who engage in NSSI and adolescents with MDD only.Methods: A total of 67 adolescents with MDD were divided into two groups based on their NSSI behavior: the NSSI group (n = 31) and an age-, gender-, and education-matched MDD group (n = 36). The Hamilton Depression Rating Scale (HAMD) was used to assess the severity of MDD. Amplitude of low-frequency fluctuation (ALFF) analysis was used to detect alterations in local neural activity. Brain regions with aberrant neural activity were considered regions of interest (ROI). ALFF-based rs-FC analysis was used to further explore the underlying changes in connectivity between ROI and other areas in the NSSI group. Correlation analyses were performed to examine the relationship between neural changes and clinical characteristics.Results: There was no significant difference in HAMD scores between the two groups. ALFF analysis revealed that, compared to adolescents with MDD only, adolescents with MDD who engaged in NSSI displayed significantly enhanced neural activity in the right fusiform gyrus (FFG. R) and the right median cingulate and paracingulate gyri (DCG. R). Significantly reduced rs-FC of the FFG. R-bilateral medial orbital of the superior frontal gyrus (ORBsupmed. L/R)/bilateral medial superior frontal gyrus (SFGmed. L/R), FFG. R-bilateral posterior cingulate gyrus (PCG. L/R), DCG. R-left pallidum (PAL. L), DCG. R-right superior temporal gyrus (STG. R), and DCG. R-right postcentral gyrus (PoCG. R)/right inferior parietal lobule (IPL. R) was found in adolescents with MDD who were engaged in NSSI. Additionally, no significant correlations were observed between ALFF or rs-FC values and the HAMD scores between the two groups.Limitations: Owing to the cross-sectional design, the alterations in ALFF and rs-FC values in the FFG. R and DCG. R could not demonstrate that it was a state or feature in adolescents with MDD who engaged in NSSI. Additionally, the sample size was relatively small.Conclusions: This study highlights changes in regional brain activity and remote connectivity in the FFG. R and DCG. R in adolescents with MDD who engage in NSSI. This could provide a new perspective for further studies on the neurobiological mechanism of NSSI behavior in adolescents with MDD.

Dissociating default mode network resting state markers of suicide from familial risk factors for depression.

Neural signatures of suicide risk likely reflect a combination of specific and non-specific factors, and clarifying specific factors may facilitate development of novel treatments. Previously, we demonstrated an altered pattern of resting state connectivity between the dorsal and ventral posterior cingulate cortex (d/vPCC) and the dorsal anterior cingulate cortex (dACC), as well as altered low frequency oscillations in these regions, in individuals with a history of suicidal thoughts and behaviors (STBs) compared to healthy controls. It remains uncertain, however, whether these markers were directly related to STBs or, more generally, reflect a trait-level risk factor for depression. Here, we examined data from a 3-generational longitudinal study of depression where resting state fMRI data were analyzed from 2nd and 3rd generation offspring of probands with (FH+ = 44: STB+ = 32, STB- = 12) and without (FH- = 25: STB+ = 15, STB- = 10) a family history of major depressive disorder (MDD). Standard seed-based methods and a frequency-based analysis of intrinsic neural activity (ALFF/fALFF) were employed. FH of MDD, but not a personal history of STBs or MDD, was associated with relatively reduced dPCC-dACC, and enhanced vPCC-dACC functional connectivity. FH of MDD showed a pattern of reduced ALFF in the dPCC whereas an STB history was associated with an increase. All findings were invariant to confounding by lifetime MDD and current depression severity. Overall, contrary to predictions, resting state functional connectivity within the default mode network (DMN) was associated with FH of depression rather than STBs. These findings confirm the relevance of DMN functional connectivity for mood disorders and underscore the importance of disambiguating biological factors that differentially relate to mental disorders versus STBs.

Evaluation of depression and anxiety control in greek patients with major depressive disorder with/without generalized anxiety disorder and cardiovascular disease–pronoi study

IntroductionPatients with depression are likely to eventually develop Cardiovascular disease(CVD) and have a higher mortality rate than general population. In addition, anxiety disorders, especially Generalized Anxiety Disorder (GAD), may be associated with mortality and other adverse cardiac outcomes.ObjectivesEvaluation of depression and anxiety control in Greek patients with Major Depressive Disorder (MDD) with/without GAD and CVD, under 6 months of treatment with citalopram, and/or quetiapine, and/or pregabalin.Methods565 patients with MDD with/without GAD, enrolled in this observational, study (NCT03317262). The subgroup of 133(24%) patients had CVD. Severity of MDD and GAD symptoms was evaluated using the HAM-D and HAM-A Scores at baseline (V1) and after 6 months (V3) respectively.ResultsMean HAM-D score in patients with CVD without GAD, at V1 and V3 was 23.94±7.51 and 8.14±4.65 respectively (p&lt;0.0001). Similar results were observed in patients without CVD without GAD (HAM-D score 26.67±8.79 at V1 and 7.44±4.40 at V3). Mean HAM-A score in patients with CVD and GAD at V1 and V3 was 25.64±6.38 and 8.98±3.93, respectively (p&lt;0.0001). Same magnitude reduction in HAM-A score was observed in patients without CVD and GAD, 26.27±8.16 at V1 and 9.28±6.48 at V3 (p&lt;0.0001). Patients’ depression symptoms with/without CVD and GAD showed also a significant reduction between V1 and V3.ConclusionsMDD patients with CVD without GAD, had a marginally lower baseline HAM-D score versus patients with GAD. After 6 months of treatment with citalopram, and/or quetiapine, and/or pregabalin the improvement of depressive and anxiety symptoms was almost equal between MDD patients with/without GAD regardless of the presence of coexisting CVD.DisclosureEmployee of ELPEN Pharmaceutical Co. Inc.

Childhood trauma influences the age of onset and severity of major depressive disorder via brain function

IntroductionAssociations between childhood trauma (CT), social support (SS), brain functions and major depressive disorder (MDD) is unknown.ObjectivesThis study aimed to investigate whether brain functions mediated associations between CT, SS, and MDD.Methods164 MDD and 98 healthy controls (HC) were recruited and measured by HAMD-24 and HAMA. Some completed CT questionnaire (CTQ) and social support rating scale (SSRS). We examined amplitude of low-frequency fluctuation (ALFF) between the two groups and correlations between HAMD-24, HAMA and ALFF in MDD. Then, the peak voxels of the ALFF changed regions were used as seeds to analyze whole-brain functional connectivity (FC). Next, correlations between FC and clinical variables of MDD were performed. Last, mediation analysis was used to further determine whether ALFF or FC could mediate the associations between CT, SS, and different clinical variables in MDD patients.ResultsCompared to HC, MDD showed decreased ALFF in right posterior cingulate (PCC_R), left postcentral gyrus, right precentral gyrus, and left thalamus (THA_L), but increased ALFF in right medial frontal gyrus, left subgenual anterior cingulate, and left middle occipital gyrus as well as decreased FC in bilateral PCC and THA_R. HAMD-24 had negative correlation with ALFF of THA_L, while positive with sexual abuse (SA) score in MDD. Mediation analysis revealed that FC of PCC_R mediated association between SA and baseline HAMD-24, and itself or together with SS mediated association between CT and onset age of MDD.ConclusionsCT may influence the depression severity and onset age of MDD by moderating FC of PCC_R only or together with SS.

Depression and worry symptoms predict future executive functioning impairment via inflammation.

Scar models posit that heightened anxiety and depression can increase the risk for subsequent reduced executive function (EF) through increased inflammation across months. However, the majority of past research on this subject used cross-sectional designs. We therefore examined if elevated generalized anxiety disorder (GAD), major depressive disorder (MDD), and panic disorder (PD) symptoms forecasted lower EF after 20 months through heightened inflammation. Community-dwelling adults partook in this study (n = 614; MAGE = 51.80 years, 50% females). Time 1 (T1) symptom severity (Composite International Diagnostic Interview - Short Form), T2 (2 months after T1) inflammation serum levels (C-reactive protein, fibrinogen, interleukin-6), and T3 (20 months after T1) EF (Brief Test of Adult Cognition by Telephone) were assessed. Structural equation mediation modeling was performed. Greater T1 MDD and GAD (but not PD) severity predicted increased T2 inflammation (Cohen's d = 0.21-1.92). Moreover, heightened T2 inflammation forecasted lower T3 EF (d = -1.98 to -1.87). T2 inflammation explained 25-32% of the negative relations between T1 MDD or GAD and T3 EF. T1 GAD severity predicting T3 EF via T2 inflammation path was stronger among younger (v. older) adults. Direct effects of T1 MDD, GAD, and PD forecasting decreased T3 EF were found (d = -2.02 to -1.92). Results remained when controlling for socio-demographic, physical health, and lifestyle factors. Inflammation can function as a mechanism of the T1 MDD or GAD-T3 EF associations. Interventions that successfully treat depression, anxiety, and inflammation-linked disorders may avert EF decrements.

Individual Differences in Response to Antidepressants

Antidepressants are commonly used to treat major depressive disorder (MDD). Antidepressant outcomes can vary based on individual differences; however, it is unclear whether specific factors determine this variability or whether it is at random. To investigate the assumption of systematic variability in symptomatic response to antidepressants and to assess whether variability is associated with MDD severity, antidepressant class, or study publication year. Data used were updated from a network meta-analysis of treatment with licensed antidepressants in adults with MDD. The Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, and PsycInfo were searched from inception to March 21, 2019. Additional sources were international trial registries and sponsors, drug companies and regulatory agencies' websites, and reference lists of published articles. Data were analyzed between June 8, 2020, and June 13, 2020. Analysis was restricted to double-blind, randomized placebo-controlled trials with depression scores available at the study's end point. Baseline means, number of participants, end point means and SDs of total depression scores, antidepressant type, and publication year were extracted. Log SDs (bln σ̂) were derived for treatment groups (ie, antidepressant and placebo). A random-slope mixed-effects model was conducted to estimate the difference in bln σ̂ between treatment groups while controlling for end point mean. Secondary models determined whether differences in variability between groups were associated with baseline MDD severity; antidepressant class (selective serotonin reuptake inhibitors and other related drugs; serotonin and norepinephrine reuptake inhibitors; norepinephrine-dopamine reuptake inhibitors; noradrenergic agents; or other antidepressants); and publication year. In the 91 eligible trials (18 965 participants), variability in response did not differ significantly between antidepressants and placebo (bln σ̂, 1.02; 95% CI, 0.99-1.05; P = .19). This finding is consistent with a range of treatment effect SDs (up to 16.10), depending on the association between the antidepressant and placebo effects. Variability was not associated with baseline MDD severity or publication year. Responses to noradrenergic agents were 11% more variable than responses to selective serotonin reuptake inhibitors (bln σ̂, 1.11; 95% CI, 1.01-1.21; P = .02). Although this study cannot rule out the possibility of treatment effect heterogeneity, it does not provide empirical support for personalizing antidepressant treatment based solely on total depression scores. Future studies should explore whether individual symptom scores or biomarkers are associated with variability in response to antidepressants.

LEVEL OF C-REACTIVE PROTEIN AMONG PATIENTS WITH MAJOR DEPRESSIVE DISORDER

Background: The relationship between inflammation and major depressive disorder (MDD) and its associated suicide has been widely debated in recent years. MDD is one of the most common psychiatric disorders, effects on about 6.7% of adult in every year and it is also one of major causes of suicide. C-reactive protein (CRP) is one of signs of inflammation in body and may have a role as an inflammatory marker in depression and associated suicide. Objective: To find the association between depression and C-reactive protein. Patients and Methods: The sample consisted of 25 adult diagnosed with MDD, and 15 adult were not diagnosed with any mental disorder. They were diagnosed clinically according to DSM-5 through a designed semi structured clinical interview and through application of Beck Depression Inventory-II (BDI-II) and Suicidal Probability Scale (SPS), and blood samples were taken to measure plasma level of CRP. Results: There was a relationship between major depressive disorder and C-reactive protein where it was found that there were statistically significant differences between the cases and control groups in scores of CRP. The mean of cases were 3.88mg/L and control group was 3mg/L with P value 0.019. Moreover, there was a statistically significant difference between CRP level and degree of severity of depression on BDI-II scale. Besides that, there was a relationship in CRP of cases group when compared between depression with suicide ideations and without, yet not a statistically significant. There were also statistically significant differences between cases and controls groups on BDI-II and also on Suicidal Probability Scale (SPS). Conclusion: C-reactive protein elevated in major depressive disorder patients, and also associated with severity of MDD although this elevation lie in normal range of CRP.